DJ-1 is an antioxidant protein that has been implicated in autosomal recessive Parkinson’s disease (PD), although the mechanism by which DJ-1 deficiency causes PD remains elusive. Drosophila DJ-1 mutants are highly sensitive to oxidative stress and UV irradiation, and oxidative stress-induced cell death is significantly increased in dopaminergic neurons. In this study, we characterized a Drosophila homologue of death domain-associated protein (Daxx), Daxx-like protein (DLP), as a key player in the process of the oxidative stress-induced cell death in DJ-1 mutants. Upon oxidative stress, DLP expression was increased in the DJ-1 mutants, and locomotive defects and oxidative stress-induced phenotypes including apoptosis and lethality were dramatically rescued by DLP deficiency. More interestingly, we revealed that Drosophila forkhead box subgroup O was required for the increased DLP expression in DJ-1 mutants. Additionally, Drosophila DJ-1 suppressed DLP and Daxx translocation from the nucleus to the cytosol in both fly brain and mammalian cells. Interestingly, targeted expression of Drosophila DJ-1 to mitochondria efficiently inhibited Daxx translocation. Our results show that Drosophila DJ-1 protects dopaminergic neurons from oxidative stresses by regulating the subcellular localization and gene expression of DLP, providing a clue to understanding the molecular mechanism underlying oxidative stress-induced neuronal death in PD.
- 2014–Present Professor, Konkuk University, Seoul, Korea
- 2011 Visiting Professor, University of California at San Francisco
- 2010-2014 Associate Professor, Konkuk University, Seoul, Korea
- 2009-2010 Manager, the Genetics Society of Korea
- 2008-2010 Manager, Korean Society for Drosophila Research
- 2005-present Fellow, the Genetics Society of Korea
- 2005-present Fellow, Korean Society for Molecular and Cellular Biology
- 2005-2010 Assistant Professor, Konkuk University, Seoul, Korea
- 2003-2005 Post-doc Fellowship, Baylor College of Medicine, Houston, TX
- 2003 Overseas Post-doctoral Fellowships, Korea Science and Engineering Foundation
- 2000-2003 Post-doc Fellowship, Korea Advanced Institute of Science and Technology
- 2000 Ph.D., Seoul National University, Seoul, Korea
- 1995 Master, Seoul National University, Seoul, Korea
- 1995 Field study fellowships for young scientist program, Korea Science and Engineering Foundation
- 1993 B.A., Seoul National University, Seoul, Korea
- Jeong H, Han SY, Lee M, Lee S, Shin M, Jeon Y, Lee K, Cho KS (2015) Roles of Tsp66E and Tsp74F in border cell migration and the maintenance of border cell adhesion in Drosophila. Genes & Genom. 37:559-565.
- Lee S, Bang SM, Lee JW, Cho KS (2014) Evaluation of traditional medicines for neurodegenerative diseases using Drosophila models. Evid Based Complement Alternat Med. 2014:967462.
- Hong YK, Lee D, Hwang S, Bang SM, Jeong H, Choi S, Phamd T-V, Kang L-W, Lee Y-H, Cho KS, Cha G-H (2014) The role of serine 190 in FOXO nuclear export and cell death induction in (Drosophila melanogaster). Genes & Genom. 36:475-483.
- Hwang S, Song S, Hong YK, Choi G, Suh YS, Han SY, Lee M, Park SH, Lee JH, Lee S, Bang SM, Jeong Y, Chung WJ, Lee IS, Jeong G, Chung J, Cho KS. (2013) Drosophila DJ-1 decreases neural sensitivity to stress by negatively regulating Daxx-like protein through dFOXO. PLoS Genet. 9(4):e1003412. doi: 10.1371/journal.pgen.1003412
- Park SH, Lee S, Hong YK, Hwang S, Lee JH, Bang SM, Kim YK, Koo BS, Lee IS, Cho KS. (2013) Suppressive effects of SuHeXiang Wan on Aβ42-induced extracellular signal-regulated kinaseERK hyperactivation and glial cell proliferation in a transgenic Drosophila model of Alzheimer’s disease. Biol Pharm Bull. 36(3):390-398.
- Han SY, Lee M, Hong YK, Hwang S, Choi G, Suh YS, Park SH, Lee S, Lee SH, Chung J, Baek SH, Cho KS.(2012) Tsp66E, the Drosophila KAI1 homologue, and Tsp74F function to regulate ovarian follicle cell and wing development by stabilizing integrin localization. FEBS Lett. Nov 16;586(22):4031-4037.
- Baradaran-Heravi A, Raams A, Lubieniecka J, Cho KS, DeHaai KA, Basiratnia M, Mari PO, Xue Y, Rauth M, Olney AH, Shago M, Choi K, Weksberg RA, Nowaczyk MJ, Wang W, Jaspers NG, Boerkoel CF. (2012) SMARCAL1 deficiency predisposes to non-Hodgkin lymphoma and hypersensitivity to genotoxic agents in vivo. Am J Med Genet A. Sep;158A(9):2204-2213.